Prevention of Perioperative Infection · Prevention of Perioperative Infection By Nicholas Fletcher, MD, D’Mitri Sofianos, BS, Marschall Brantling Berkes, BS, and William T. Obremskey,

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2007;89:1605-1618. doi:10.2106/JBJS.F.00901 J Bone Joint Surg Am.Nicholas Fletcher, D'Mitri Sofianos, Marschall Brantling Berkes and William T. Obremskey

Prevention of Perioperative Infection

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Current Concepts Review

Prevention of Perioperative InfectionBy Nicholas Fletcher, MD, D’Mitri Sofianos, BS, Marschall Brantling Berkes, BS, and William T. Obremskey, MD, MPH

Investigation performed at Vanderbilt Orthopedic Trauma, Nashville, Tennessee

➤ Administration of preoperative antibiotics is associated with reduced rates of surgical site infections.

➤ Antibiotics should be continued for no longer than twenty-four hours after elective surgery or surgical treat-ment of closed fractures.

➤ Chlorhexidine gluconate is superior to povidone-iodine for preoperative antisepsis for the patient and surgeon.

➤ Closed suction drainage is not warranted in elective total joint replacement. It is associated with an increasedrelative risk of transfusions. Drains left in situ for more than twenty-four hours are at an increased risk for bac-terial contamination.

➤ The rate of postoperative infections associated with occlusive dressings is lower than that associated withnonocclusive dressings.

➤ Appropriate management of blood glucose levels, oxygenation, and the temperature of the patient reducesthe risk of postoperative infection.

urgical site infection is one of the most common compli-cations that a surgeon encounters, with an infection oc-curring after approximately 780,000 operations in the

United States each year1. In the era of evidence-based medi-cine, it is in the best interest of patients and physicians to fol-low practices backed by basic science and clinical data.Unfortunately, standards of practice, even for the use of pro-phylactic antibiotics, are frequently not followed2. In 2005,this journal made a commitment to present physicians withthe literature to support the best available treatment for theirpatients with use of “recommendations for care” based ongrades of recommendation in review articles3. Grades of rec-ommendation are intended to guide surgeons in determiningwhether they should change their practice on the basis of good(Grade-A) or fair (Grade-B) recommendations. Grade-A rec-ommendations are generated from Level-I studies, whereasGrade-B recommendations are derived from Level-II or III re-search. A proposal is considered to be Grade C when there ispoor or conflicting evidence concerning an intervention based

on Level-IV or V studies, and Grade I indicates that evidenceis inadequate to make a recommendation4. We have providedthese recommendations in this article, and we have also pro-vided a level-of-evidence grade for individual studies. Meth-ods for determining levels of evidence were introduced in thisjournal in 2003 and have been shown to be reliable andreproducible5,6.

The current article synthesizes the best available evi-dence regarding use of preoperative antibiotics before electiveand emergent orthopaedic operations, preoperative skin prep-aration of the patient and surgeon, operating-room issues,wound closure, operative drainage, and use of dressings in thehope that it will help physicians to reduce the incidence ofpostoperative wound infection. The management and effect ofimportant patient factors such as smoking, nutritional status,immunocompromise, medications, cardiovascular status, obe-sity, and other major comorbidities will not be addressed here.The reader is instead referred to an excellent review of thesetopics by Gurkan and Wenz7.

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Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor amember of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercialentity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical prac-tice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

J Bone Joint Surg Am. 2007;89:1605-18 • doi:10.2106/JBJS.F.00901

Fletcher_CCR.fm Page 1605 Friday, June 8, 2007 1:58 PM

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THE JOU R N A L OF BO N E & JO I N T SU RG ER Y · JB JS .ORG

VO LUM E 89-A · NUM BE R 7 · JU LY 2007PRE VE N T ION OF PER I OP E R A T IVE IN F E C T I O N

Antibiotic IssuesProven Benefits of Antimicrobial Prophylaxis

he use of antibiotic prophylaxis in orthopaedic surgeryhas been shown to be beneficial. Initially, there was some

debate about whether antibiotics administered prior to sur-gery would be of any benefit or worth the risk8. Multiple pro-spective, double-blind studies support the use of antibioticprophylaxis in the settings of closed fractures and total jointarthroplasty9-16 (see Appendix).

The benefits of antibiotic prophylaxis have been sub-stantiated in studies of open fractures, for which antibioticshave been shown to be effective as long as they target the usualinfecting organisms17. In a prospective randomized trial,Patzakis and Wilkins found that the preoperative administra-tion of appropriate antibiotics was the most important factorin determining the rate of wound infection in association withopen fractures18. The Cochrane Database of Systematic Re-views also endorses the practice of treating open fractureswith prophylactic antibiotics19.

Choice of AntibioticBacterial contamination and eventual infection most oftencome from skin or airborne sources20,21. The most common or-ganisms that cause deep wound infection are Staphylococcusaureus and coagulase-negative staphylococci such as Staphy-lococcus epidermidis20,22-24. Therefore either cefazolin or cefu-roxime should be used in conjunction with hip or kneearthroplasty, fixation of closed fractures, and most elective or-thopaedic procedures2,22,25-27.

Systemic antibiotic prophylaxis for patients with an openfracture has recently been systematically reviewed by the Surgi-cal Infection Society (SIS)28 and the Eastern Association for theSurgery of Trauma (EAST)29. Each group developed recom-mendations on the basis of the classic classification system de-scribed by Gustilo and Anderson in 1976 and the subsequentmodification by Gustilo et al. in 1984 (see Appendix)30-32. Bothanalyses28,29 provided substantial evidence that antibioticprophylaxis for type-I open fractures should include a first-generation cephalosporin. Traditional teaching has assertedthat coverage against gram-negative organisms is required forall type-III and perhaps some type-II fractures because of theincreased contamination and higher-energy mechanism asso-ciated with these fractures. A penicillin has also been added tothe prophylactic regimen for fractures at risk for clostridialcontamination33. The SIS and EAST groups differ with regardto their support of these principles. The EAST group recom-mends the use of additional coverage against gram-negativeorganisms on the basis of evidence that “gram negative organ-isms are cultured from type III wounds after initial débride-ment.”29 This statement is somewhat misleading as, to ourknowledge, no recent investigations have shown any relation-ship between the results of cultures performed at the time ofthe initial presentation and the causative bacteria grown onculture during the management of a subsequent infection34-36.The SIS group, citing the bacterial resistance patterns reportedby Patzakis et al.17 in their seminal study in 1974, failed to find

any outcomes data to support coverage against gram-negativebacteria. While two studies have shown that administration ofgentamicin once daily is effective prophylaxis for patients witha type-II or III open fracture37,38, this regimen has not beencompared with other antibiotic regimens, to our knowledge.The SIS group also suggested that penicillin G may not be theoptimal therapy for clostridial infections, citing several studiesof animals by Stevens et al.39-41, although the EAST group stillrecommends prophylaxis with penicillin for patients with afracture at risk for clostridial contamination. A Grade-A rec-ommendation can be made for the administration of a type-Icephalosporin for all open fractures. Despite their widespreaduse, there is currently insufficient evidence to support the useof aminoglycosides in the management of type-II and III openfractures. There is also not enough data to make recommenda-tions (Grade I) regarding the use of penicillin for contaminatedopen fractures. This area clearly needs to be explored further inrandomized controlled studies.

Vancomycin or clindamycin may be used for patientswith an allergy or adverse reaction to beta-lactam antibiotics.To our knowledge, no one has compared the efficacy of clin-damycin with that of vancomycin for prophylaxis against in-fection, and thus no recommendation can be made (Grade I)regarding the use of one antibiotic over the other for patientswith an allergy to beta-lactam agents. Cross reactivity betweencephalosporins and penicillins has historically been reportedto be >10%; however, this percentage has been questioned inthe recent literature because of the lack of confirmation of theallergy with skin-testing. Current data suggest a much lowerrisk of cross reactivity42. Anaphylaxis to cephalosporin is ex-ceedingly rare, with the rate ranging from 0.0001% to 0.1%43.Li et al. assessed sixty patients with a documented allergyto penicillin or cephalosporin who were evaluated preopera-tively by an allergist44. Fifty-nine of these patients were given apenicillin-allergy skin test, and 93% (fifty-five) of the fifty-nine had a negative result of that test. Ninety percent (fifty-four) of the sixty patients in the series were cleared by the al-lergist to receive a cephalosporin. No patient had an allergicreaction. Nonetheless, multiple studies have shown a four totenfold risk of cross reactivity in patients with a documentedallergy to penicillin who are subsequently given a cephalo-sporin, and more than one expert panel has recommended theuse of vancomycin for such patients28,45.

Timing of Antibiotic AdministrationAntibiotics should be administered within sixty minutesprior to the incision46,47 and, ideally, as near to the time of theincision as possible48-50. An additional intraoperative dose isadvised if the duration of the procedure exceeds one to twotimes the half-life of the antibiotic or if there is substantialblood loss during the procedure51. The American Academy ofOrthopaedic Surgeons has developed recommendations re-garding the frequency of intraoperative antibiotic adminis-tration (Table I)52. One potential method of ensuringpreoperative, and if necessary subsequent intraoperative, ad-ministration of antibiotics in hospitals in which anesthesiolo-

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gists track patients electronically is to include a computerizedalert that reminds anesthetists and surgeons to provide theappropriate antibiotics53.

Vancomycin UsageVancomycin may be used for patients with known colonizationwith methicillin-resistant Staphylococcus aureus or in facilitieswith recent outbreaks of methicillin-resistant Staphylococcusaureus infections. Vancomycin may also be used for patientswho have hypersensitivity to penicillin. Excessive use of vanco-mycin promotes the formation of resistant organisms54-59. Van-comycin should be started within two hours prior to theincision because of its extended infusion time. The infusiontime is extended to prevent the adverse reactions that aresometimes associated with vancomycin infusion, such ashypotension or chest pain mimicking myocardial infarction60.H1 and H2 histamine receptor blockers allow more rapidinfusion61,62.

Two randomized trials failed to demonstrate a benefit ofvancomycin compared with cefazolin63 or cefuroxime64 forpreventing perioperative infections, although there was alower prevalence of methicillin-resistant Staphylococcus aureusinfections in patients treated with vancomycin. Vancomycinmay be warranted for certain procedures in institutions wheremethicillin-resistant Staphylococcus aureus infection is an im-portant problem or if the patient has identifiable risk factors,such as recent hospitalization, renal disease, or diabetes2.

Duration of Antibiotic AdministrationCurrent data support minimizing the duration of antibioticadministration. The postoperative duration of routine antibi-otic use has decreased from multiple days to twenty-fourhours. Some surgeons prefer a single dose. Research by Nel-son et al. supports prophylactic antibiotic administration fortwenty-four hours after total hip or total knee arthroplasty orhip fracture surgery65. In their randomized controlled trial,358 patients received prophylactic nafcillin or cefazolin fortwenty-four hours or seven days. There was no significant dif-ference in the prevalence of surgical site infection between thegroups at six weeks or one year. Williams and Gustilo retro-spectively compared the outcomes for 1341 patients who hadreceived prophylaxis for three days following total joint ar-throplasty with those for 450 patients who had received it forone day66. An infection developed in eight (0.6%) of the 1341

patients in the first group compared with three (0.67%) of the450 in the second group. Pollard et al.67 and Mauerhan et al.23

also found that the infection risk following twenty-four hoursof antibiotic administration was no higher than that followingthree or fourteen days of administration.

A single dose of antibiotics may be adequate for prophy-laxis against perioperative infection. A randomized controlledtrial of 466 patients treated with total joint arthroplastyshowed no significant difference in the rate of surgical site in-fection between the group that had received a single dose ofantibiotics and groups that had received prophylaxis for two,three, or seven days68. The authors noted that the use of single-dose prophylaxis instead of forty-eight hours of prophylaxiswould save $7.7 million per 100,000 patients. Using antibiot-ics for two days postoperatively instead of for seven days post-operatively would save $29.7 million per 100,000 patients. In alarger randomized controlled trial of 1489 patients with aclosed fracture, Garcia et al. also demonstrated results that fa-vor the use of a single prophylactic dose69. The difference inthe infection rate among treatment groups receiving one doseof cefonicid, three doses of cefamandole, or five doses of cefa-mandole was not significant.

The proper duration of antibiotic prophylaxis for openfractures is not well established. Perhaps the lack of consensusabout the treatment protocol is due to the high variabilityamong open fractures and the poor interobserver reliability ofthe classifications of these injuries. On the basis of their exten-sive reviews, the SIS and EAST groups both recommendedthe use of prophylactic antibiotics for twenty-four hours post-operatively for patients with a type-I open fracture and forforty-eight to seventy-two hours for those with a type-III openfracture. The two groups differ with regard to their recom-mendations about the duration of antibiotic use for patientswith a type-II fracture. EAST advocates twenty-four hours ofprophylaxis, and SIS recommends forty-eight hours. The lackof data supporting longer antibiotic prophylaxis suggests thatadministration for forty-eight hours following débridementof open fractures is not clinically warranted. Two prospectiveLevel-I studies failed to show a difference in infection rates be-tween a single dose of antibiotics and intravenous administra-tion of antibiotics for five days in patients treated for an openfracture70,71. Multiple studies have shown that extending anti-biotic prophylaxis may actually increase the risk of resistantpneumonia and other systemic bacterial infections72-76.

Local AntibioticsAntibiotics may also be delivered locally, with use of impreg-nated cement beads, spacers, or premolded implants. Localantibiotic delivery requires a delivery vehicle, most com-monly polymethylmethacrylate cement, and an antimicrobialagent available in a powder form. Two to 4 g of tobramycinand 2 g of vancomycin per 70-g bag of cement are often usedbecause they are active against the most common microbesand are heat-stable. Systemic toxicity is not a concern77. Theeluted antibiotic represents a small percentage of the totalamount of antibiotic present, and elution mainly occurs dur-

TABLE I Recommendations by the American Academy of Or-thopaedic Surgeons for Repeat Doses of Antibiotics52

Antibiotic Frequency of Administration

Cefazolin Every 2-5 hours

Cefuroxime Every 3-4 hours

Clindamycin Every 3-6 hours

Vancomycin Every 6-12 hours


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ing the first twenty-four hours78,79. For a more comprehensiveanalysis of the basic science and clinical benefits of local anti-biotics in patients undergoing high-risk joint reconstruction,the reader is referred to the excellent review by Jiranek et al.80.

To our knowledge, no major prospective randomizedcontrol trials have shown a benefit to the use of local antibiot-ics compared with intravenous systemic antibiotics, but mul-tiple retrospective series have suggested benefits of localantibiotics. Henry et al. found that the use of an antibioticbead pouch decreased the prevalence of wound infection andosteomyelitis associated with open fractures; however, this in-crease was in comparison with the rate in historical controls81.Keating et al. examined the benefit of the antibiotic-bead-pouch technique in a study of eighty-one open tibial fracturestreated with intramedullary stabilization and either systemicantibiotics alone (twenty-six fractures) or a combination ofsystemic antibiotics and local tobramycin beads (fifty-fivefractures)82. They found fewer deep infections in the patientsmanaged with the combination of systemic and local antibiot-ics; however, this result was not significant (p = 0.12). Oster-mann et al. performed a retrospective review of 1085 openfractures treated with either systemic antibiotics alone (240fractures) or systemic and local antibiotics (845 fractures)83.The infection rate was significantly reduced by the use of localand systemic antibiotics (infection rate, 3.7% [thirty-one of845]) rather than systemic antibiotics alone (infection rate,12% [twenty-nine of 240]; p < 0.001). The reduction in therate of acute osteomyelitis was significant in the patients witha type-IIIB or IIIC fracture, and the reduction in the rate ofchronic osteomyelitis was significant in those with a type-II orIIIB fracture83. This study has been criticized because a dispro-portionate number of wounds were left open in the group

treated with systemic antibiotics, compared with the grouptreated with the bead pouch, potentially increasing the risk oflocal wound infection84. We are aware of only one randomizedtrial involving use of the antibiotic bead pouch85. This study, inwhich open fractures were managed with either systemic anti-biotics or local antibiotics after a single preoperative prophy-lactic dose had been given in the emergency department, didnot demonstrate a benefit in association with local adminis-tration (p > 0.05). The study was underpowered, and thefollow-up rate was only 60%.

In summary, preoperative antibiotics have become thestandard of care before the vast majority of orthopaedic proce-dures (Table II). The decision regarding whether to administeran additional dose of antibiotics intraoperatively should bebased on the half-life of the particular antibiotic. Vancomycinor clindamycin should be given to patients with a documentedallergy to penicillin. Antibiotic use should be stopped as soonas possible after the surgery; however, there is still controversyregarding the appropriate duration of antibiotic coverage in as-sociation with both elective procedures and procedures fortraumatic injuries. Anecdotal clinical and basic-science86 evi-dence supports the use of local antibiotics for patients withan open fracture; however, a large prospective randomized trialis needed to better delineate the clinical role of antibiotic-impregnated beads in this subset of skeletal injuries.

Preoperative Hair Removalreoperative shaving of the surgical site is common prac-tice, but there is a scarcity of data to support its use. Sev-

eral authors have denounced shaving on the night before theoperation because of an increased risk of surgical site infectionas a result of many microscopic cuts in the epidermis, which

P

TABLE II Recommendations for Perioperative Administration of Antibiotics3

Grade of Recommendation Recommendations

A Broad-spectrum antibiotics should be administered within one hour of incision time and may be contin-ued up to twenty-four hours postoperatively. Longer antibiotic prophylaxis is not warranted in elective procedures or closed fracture care

Patients with an open fracture should receive antibiotics urgently, and administration should be contin-ued for twenty-four hours postoperatively. A first-generation cephalosporin should be used for all open fractures when not otherwise contraindicated

B Vancomycin appears to be equivalent to a first-generation cephalosporin in the prevention of periopera-tive infection when there is no history of methicillin-resistant Staphylococcus aureus infection

C Local antibiotics may help reduce the rate of infection and osteomyelitis in association with open fractures

Vancomycin may be used as antibiotic prophylaxis in patients with a beta-lactam allergy

I Aminoglycosides may decrease the prevalence of infection in association with Gustilo and Anderson type-II and III open fractures

There is inadequate evidence to support the use of penicillin to prevent clostridial infection in patients with a severely contaminated open fracture

There is inadequate evidence to suggest that either clindamycin or vancomycin is superior to the other for antibiotic prophylaxis in patients with beta-lactam allergy


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harbor bacteria87. Clippers do not come into contact with theskin itself and have been associated with a reduction in post-operative infection rates88-90. A meta-analysis by the Cochranegroup showed that the relative risk of a surgical site infectionfollowing hair removal with a razor was significantly higherthan that following hair removal with clippers (relative risk,2.02; 95% confidence interval, 1.21 to 3.36)91. Furthermore,the analysis showed no difference in the rate of postoperativeinfections between procedures preceded by hair removal andthose performed without hair removal. Whenever hair is re-moved, clippers, rather than a razor, should be used at thetime of surgery (Table III)92.

Preoperative Skin AntisepsisPatients

he most commonly used antiseptic agents for surgicalscrubbing include chlorhexidine gluconate, alcohol-based

solutions, and iodophors such as povidone-iodine. Chlor-hexidine gluconate acts to disrupt the cellular membranes ofbacteria and is favored for its long-lasting activity againstgram-positive and gram-negative organisms found on humanskin. The iodophors also act against common skin flora; how-ever, their activity is much shorter than that of chlorhexidinegluconate. Chlorhexidine gluconate and povidone-iodine bothreduce bacterial counts on contact; however, this effect is sus-tained longer in skin cleaned with chlorhexidine. Furthermore,unlike chlorhexidine gluconate, the iodophors can be inacti-vated by blood or serum proteins and should be allowed to dryin order to maximize their antimicrobial action93. Alcohol is anexcellent antimicrobial and has germicidal activity against bac-teria, fungi, and viruses. The effectiveness of pure alcohol solu-tions is limited by their lack of any residual activity and theirflammability (see Appendix). A recent meta-analysis showedno difference in efficacy among skin antiseptics used in cleansurgery; however, the rarity of infection in such situationsprobably explains the low power of the included studies94.

Foot and ankle surgery is often complicated by infection

due to local contamination95,96. Infection rates associated withankle arthrodesis have been as high as 19%97, whereas fusion ofthe subtalar joint is followed by an infection approximately 6%of the time95,98. Between 36% and 80% of cultures of specimenstaken from the forefoot after preparation with a povidone-iodine scrub and paint are positive compared with 0% to 28%of cultures of specimens taken from the anterior aspect of theankle after such preparation99,100. Ostrander et al. found fewerbacteria on feet prepared with ChloraPrep (2% chlorhexidinegluconate and 70% isopropyl alcohol; Medi-Flex, OverlandPark, Kansas) than on those prepared with DuraPrep (0.7%iodin and 74% isopropyl alcohol; 3M Healthcare, St. Paul,Minnesota) or Techni-Care (3.0% chloroxylenol; Care-TechLaboratories, St. Louis, Missouri)101. There was no difference ininfection rates among the three groups. Keblish et al. quantita-tively assessed skin contamination on feet cleaned with one offour methods: a povidone-iodine paint and scrub, a povidone-iodine paint and scrub after an isopropyl alcohol scrub,povidone-iodine scrub brushing, and isopropyl alcohol scrubbrushing100. There were significantly fewer positive cultures ofspecimens from hallucal folds of the feet prepared with the iso-propyl alcohol scrub brushing (12% compared with 76% forthe group prepared with povidone-iodine scrub brushing, p <0.001). The use of a brush to apply the cleansing agent was alsosuperior to the use of a standard applicator in reducing thenumber of positive cultures of specimens from web spaces.

In vitro studies have provided strong evidence thatpovidone-iodine may impair wound-healing. Cooper et al.evaluated the toxicity of common wound irrigants with use of aproven cell-viability assay and found povidone-iodine, even inconcentrations of 0.5% (1/20th) of those used in clinical prac-tice, to be extremely toxic to fibroblasts and keratinocytes102.Thus, povidone-iodine should not be used for preparation ofopen wounds or on postoperative dressings103.

The current literature strongly suggests that chlorhexi-dine gluconate is superior to povidone-iodine for preoperativeantisepsis for patients (Table III). Alcohol is an excellent antimi-

T

TABLE III Recommendations for Patient Preparation and Surgical Scrubs


A Compared with povidone-iodine, chlorhexidine surgical scrub provides a prolonged reduction in skin con-tamination with less toxicity and skin irritation

Aqueous surgical hand-rubs are equivalent to traditional surgical scrubs with regard to their ability to re-duce bacterial contamination. Surgeons comply with hand-rub protocols better than they comply with surgical scrub protocols

A patient’s temperature, oxygenation, and serum blood glucose level should be optimized in the peri-operative period

B The use of iodophor-impregnated surgical drapes decreases skin contamination but does not appear to reduce infection rates

The use of laminar flow in the operating room is associated with decreased rates of wound infections and wound contamination

Hair removal preoperatively should be minimized and, if necessary, performed with clippers or depila-tory products


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crobial, but its benefit is limited by its lack of residual activity.Use of a combination of chlorhexidine gluconate and alcohol isperhaps a way to take advantage of their antiseptic properties.

SurgeonThe current choices of antiseptic for the surgeon scrub mimicthose used for the patient scrub. Aly and Maibach comparedthe antibacterial efficacy of a two-minute scrub with chlo-rhexidine gluconate with the efficacy of a two-minute scrubwith povidone-iodine at three time-points: immediately af-ter scrubbing, three hours later, and six hours later93. Chlo-rhexidine gluconate achieved significantly (p < 0.01) greateradjusted mean log bacterial count reductions than did povi-done-iodine at all sampling times.

Parienti et al. compared the effectiveness of aqueous al-cohol hand-rubs with that of traditional povidone-iodine orchlorhexidine gluconate scrubbing with a scrub brush before4387 clean or clean-contaminated operations104. There was nodifference in wound infection rates (2.44% for the alcoholgroup compared with 2.48% for the povidone-iodine or chlo-rhexidine gluconate group), but physician compliance withthe alcohol protocol was better than that with the other proto-col (44% compared with 28%; p = 0.008), and there werefewer complaints about skin dryness and irritation. Theseclinical findings were substantiated by Bryce et al.105. Larson etal. also compared an alcohol rub with an antiseptic scrub intheir study of twenty-five physicians106. Beginning on day 5 ofthe study, the bacterial counts yielded by the scrubless prepa-ration (containing 61% ethyl alcohol, 1% chlorhexidine glu-conate, and emollients) were found to be significantlydecreased compared with those yielded by the traditionalscrub containing 4% chlorhexidine gluconate. The alcoholrub also decreased skin damage (p = 0.002) and required lesstime (p < 0.0001) than the traditional chlorhexidine gluconatescrub. Pereira et al. also showed that prolonged use of alcoholand chlorhexidine gluconate rubs had better antibacterial effi-cacy than both traditional povidone-iodine and traditionalchlorhexidine gluconate scrubbing regimens107.

Grabsch et al. compared the traditional povidone-iodine scrub with a regimen that involved a traditional chlor-hexidine gluconate scrub plus a chlorhexidine gluconate-alcoholrub108. The authors reported that bacterial counts immedi-ately after scrubbing were reduced to a greater extent in thechlorhexidine gluconate treatment arm than in the povidone-iodine treatment arm (p < 0.001), a finding most likely due tothe additional rapid action of alcohol in the chlorhexidine glu-conate protocol. A persistent and cumulative antimicrobialeffect was also found with a repeated chlorhexidine gluconate-alcohol rub prior to any additional operations (p < 0.001).A cross-over trial conducted by Nishimura directly com-pared povidone iodine-ethanol and chlorhexidine glucon-ate-ethanol brushless scrubs after an initial povidone-iodinebrushless scrub109. The reduction in the bacterial count in thepovidone iodine-ethanol group was significantly higher thanthat in the chlorhexidine gluconate-ethanol group immedi-ately after washing (p < 0.001), but it was roughly equivalent

two hours later. This finding illustrates the more rapid anti-septic effects of povidone-iodine and/or the longer-lastingeffects of chlorhexidine gluconate. Most data indicate thatpovidone-iodine and chlorhexidine gluconate have equal effi-cacy in decreasing the initial bacterial contamination of theskin of a patient or surgeon, but chlorhexidine gluconate has alonger effect, is less toxic in open wounds, and causes less skinirritation with prolonged use (see Appendix)106-108.

Chlorhexidine gluconate-based surgical scrubs decreaseskin colony counts. Traditional scrub brushes or combinationaqueous alcohol rubs are equally efficacious. Physicians’ com-pliance with the use of aqueous rubs may be better than theircompliance with regimens requiring the use of scrub brushes(Table III).

Occlusive Drapesoban iodophor-impregnated plastic drapes (3M HealthCare) have been shown in the critical care and obstetrical

literature to reduce postoperative wound contamination asmeasured by positive cultures of specimens obtained from theskin110,111. The orthopaedic literature pertaining to iodophor-impregnated drapes has shown a reduction in wound contam-ination without any concurrent decrease in wound infection.Ritter and Campbell found no difference in wound infectionrates following 649 total joint replacements for which prep-aration was performed with either an iodine spray or acombination of alcohol and an Ioban drape112. In a recent ran-domized controlled trial, Jacobson et al. evaluated the use ofan Ioban drape in conjunction with either 3M DuraPrep Sur-gical Solution or povidone-iodine scrub and found no signifi-cant difference in wound contamination between the twogroups113. The use of impregnated plastic drapes does not ap-pear to reduce the prevalence of infection (Table III).

Irrigationound irrigation removes debris, foreign material, andblood clots while decreasing bacterial contamination.

Several in vitro and in vivo studies have shown that high-pressure pulsatile lavage is more effective than low-pressurepulsatile lavage for removing particulate matter, bacteria, andnecrotic tissue. This effect is more pronounced in contami-nated wounds treated in a delayed manner114-117. There is sub-stantial concern, however, that high-pressure pulsatile lavageand low-pressure pulsatile lavage result in higher rates of deepbacterial seeding in bone than does brush and bulb-syringe la-vage and that higher irrigant pressures result in greater os-seous damage and perhaps impairment of osseous healing.Kalteis et al. showed that high-pressure pulsatile lavage wassuperior to low-pressure pulsatile lavage and manual rinsingand was as effective as brush cleaning in removing Escherichiacoli from human femoral heads in vitro118. The study also re-vealed that, compared with brush and bulb-syringe lavage,high and low-pressure pulsatile lavage resulted in significantly(p < 0.001) higher rates of deep bacterial seeding in bone. Us-ing an in vitro contaminated human tibial fracture model,Bhandari et al. also showed that high-pressure pulsatile lavage

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results in bacterial seeding of the medullary canal119. High-pressure pulsatile lavage successfully removed almost 99% ofthe bacterial burden at the fracture surface; however, there wasa higher number of positive bacterial cultures of specimensobtained between 1 and 4 cm from the fracture site than therewere in nonirrigated controls (p < 0.01).

Similar bacterial seeding may be seen in muscle tissueafter pulsatile irrigation. Hassinger et al. showed that ovinemuscle samples subjected to high-pressure pulsatile lavagehad a significantly greater depth of bacterial penetration andgreater numbers of colonizing bacteria when compared withsamples subjected to low-pressure pulsatile lavage (p <0.05)120. Bhandari et al. found that both high and low-pressurepulsatile lavage removed bacteria for up to three hours afterthe initial contamination; however, high-pressure pulsatilelavage was more effective after this time (p < 0.05)121. High-pressure pulsatile lavage was also shown to increase muscledamage and decrease particulate removal when it was com-pared with bulb-suction irrigation in vitro122.

Recent studies have suggested that high-pressure pulsa-tile lavage may also damage the architecture of cancellous bone.Dirschl et al. found that high-pressure irrigation of osteoto-mized rabbit femora decreased the amount of new bone forma-tion during the first week following a distal femoral osteotomycompared with that seen after bulb-syringe irrigation123. Thisdifference became negligible during the second week after theosteotomy. In a rat model, high-pressure pulsatile lavage de-creased the mechanical strength of a fracture callus during thefirst three weeks of fracture-healing compared with that ob-served following bulb-syringe irrigation (p < 0.05)124.

Previous reviews have suggested that high-pressure pul-satile lavage should perhaps be reserved for severely contami-

nated wounds or for open injuries for which treatment will bedelayed. Low-pressure irrigation should be used if contamina-tion is minimal or treatment is immediate. Although Anglensuggested the use of 3 L of irrigation fluid for type-I open frac-tures, 6 L for type-II, and 9 L for type-III125, these recommen-dations have not been supported by clinical data.

Recent studies comparing the efficacy of antibiotic solu-tions with that of detergent irrigants have made a strong casefor the incorporation of detergents in wound irrigation. De-tergents such as castile soap or benzalkonium chloride are ef-fective in decreasing the burden of bacteria in musculoskeletalwounds because of their surface-active properties. The deter-gents act by disrupting hydrophobic and electrostatic forces,thereby inhibiting the ability of bacteria to bind to soft tissueand bone. In an in vitro study by Anglen et al., castile soap wassuperior to antibiotic-containing irrigants and normal salinesolution when it came to removing bacteria from steel, tita-nium, muscle, and bone126. In vivo rat studies have shown thatcastile soap is very effective in preventing Pseudomonas aerugi-nosa infection, and benzalkonium chloride was most effectiveagainst Staphylococcus aureus127. Wounds irrigated with benza-lkonium chloride alone have a higher risk of dehiscence andbreakdown. This led to the development of a sequential irriga-tion protocol involving castile soap, saline solution, benzalko-nium chloride, and a final saline solution rinse, which wasmore effective than saline solution irrigation without thecomplications of wound breakdown seen with benzalkoniumchloride alone128. Anglen conducted a prospective, random-ized study of 458 lower-extremity open fractures in which hecompared castile soap irrigation with bacitracin irrigation129.There was no significant difference between groups with re-spect to the rate of surgical site infection or bone-healing de-

TABLE IV Recommendations Regarding Surgical Drains and Wound Management


A Use of surgical drains in joint replacement surgery or closed fracture care is associated with more blood transfusions but not with any increase in the rate of hematomas, wound infections, reopera-tions, or thromboembolic disease or in the hospital stay, when compared with operations performed without a drain

The rate of surgical site infection associated with occlusive dressings is lower than that associated with nonocclusive dressings

B Surgical dressings may be removed as early as the first postoperative day without any apparent in-crease in the risk of infection

Triple antibiotic ointment increases epithelialization and has been associated with fewer infections in uncomplicated clean surgical wounds

I High-pressure pulsatile lavage removed more debris than did low-pressure pulsatile or bulb-syringe lav-age in an animal model, although the higher pressure may cause damage to bone and muscle

Castile soap irrigation appears to remove more bacteria than bacitracin does and may be associated with fewer wound-healing problems in an animal model

There is no apparent difference among wound closure techniques with regard to the rate of wound infections

There is insufficient evidence to support or refute the benefits of closure of dead space in patients un-dergoing orthopaedic surgery


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lay, but the fractures irrigated with bacitracin were associatedwith a significantly higher rate of wound-healing problems(9.5%, nineteen of 199 fractures) than were those irrigatedwith castile soap (4%, eight of 199 fractures; p = 0.03).

Irrigation of wounds and, in particular, open fracturesplays an important role in the reduction of infection (TableIV). Use of a low-to-intermediate pressure setting minimizesbone and soft-tissue damage while allowing removal of bacte-ria and particulate matter. Irrigation with castile soap im-proves organic removal and may be associated with fewerproblems with wound-healing when compared with irrigationwith antibiotic solution.

Postoperative Drainsrains have traditionally been used in an attempt to de-crease the formation of a postoperative hematoma and

manage dead space while providing a conduit for the egress ofmaterial from the wound. Studies of animals have shownmore retrograde bacterial migration with the use of simpleconduit drains than with the use of closed suction drains130.Sorensen and Sorensen evaluated 489 clean orthopaedic pro-cedures, including those performed for hip fractures and hipand knee arthroplasties, in a prospective cohort study131. Fifty-six drain tips (11%) were found to be contaminated as evi-denced by a positive culture; however, only five patients (1%)were infected by the same bacteria as had grown on culture ofthe tip specimen. Contaminated drain tips are associated withwound infections, whereas a negative tip-specimen culture isvery rarely seen in the presence of wound infection132. Drink-water and Neil placed drains in ninety-two patients undergo-ing hip or knee arthroplasty and removed them at randomlygenerated times during the first ninety-six hours postopera-tively133. Only one contaminated drainage tip was found whenthe drain was removed in the first twenty-four hours post-operatively. Five (18%) of twenty-eight tips removed aftertwenty-four hours were found to be contaminated when a cul-ture was performed, although the difference was not signifi-cant. In a retrospective analysis of more than 73,000 surgicalpatients with a wound infection, the presence of a surgicaldrain for more than twenty-four hours was associated with ahigher likelihood that the wound would be infected withmethicillin-resistant Staphylococcus aureus than with methicillin-sensitive Staphylococcus aureus134.

The current orthopaedic literature has not shown an ad-vantage to the use of drains in elective surgery. In a recentmeta-analysis, Parker et al. evaluated the use of drains in 3689joint-replacement surgical wounds135. The data showed no dif-ference in rates of infection, wound hematomas, reoperationsfor wound complications, limb swelling, or thromboemboliccomplications and no difference in the hospital stay. Wounddrainage was associated with a higher risk of transfusion (rela-tive risk, 1.43). Two subsequent studies in the arthroplastyliterature showed no benefit of the use of drainage in jointreplacement136,137.

The use of drains in fracture surgery has not been wellevaluated. Two randomized controlled trials in which surgical

drainage was compared with closure without a drain in cleanorthopaedic procedures for traumatic injuries showed thatdrainage provided no benefit with respect to rates of infec-tion, hematomas, transfusion, or revision surgery138,139. Tworandomized studies also failed to show that the use of surgicaldrainage in elective lumbar spinal surgery reduced the rate ofcomplications, including the formation of epidural hemato-mas or the development of a neurologic deficit140,141. In sum-mary, Grade-A recommendations support the performanceof operations without the use of a surgical drain. There is noevidence to suggest that use of a surgical drain prevents for-mation of a hematoma, infection, or wound dehiscence or in-fluences other surgical outcomes (Table IV and Appendix).

Wound Closurehe literature on wound closure in orthopaedic proceduresis sparse and primarily discusses its impact on the results

of joint replacement surgery and arthroscopy portals. Com-parative studies have involved subjective analysis of the ap-pearance of the healed wound, inflammation, and patientsatisfaction. The data are insufficient to make recommenda-tions (Grade I) regarding appropriate wound-closure tech-niques (Table IV). The principle of maximizing blood flowwhile minimizing bacterial contamination and dead space hasbeen studied. In a study in which laser Doppler flowmetry wasused to evaluate cutaneous blood flow in association with var-ious suture techniques, blood flow was significantly higher onthe first postoperative day than it was on the fifth day and per-fusion in wounds closed with subcutaneous sutures wasgreater than that in wounds closed with mattress sutures orsurgical staples (p = 0.048)142.

Contaminated wounds are associated with a higher riskof wound infection. Bacterial adherence to braided sutures isthree to ten times higher than adherence to monofilamentsutures143,144. Animal models have been used to evaluate closureof contaminated wounds145. Polglase and Nayman examinedthe use of subcuticular Dexon or transdermal sutures in con-taminated wounds in an animal model146. Using the presenceof pus as the sole criterion for wound infection, they foundthat 73% of wounds that had been contaminated prior to clo-sure with silk were infected at one week in comparison with23% of wounds that had been closed with subcuticular Dexonsutures (p < 0.05).

The correct management of surgical dead space, particu-larly in the setting of gross contamination or infection, is con-troversial. Condie and Ferguson found that layered closureimproved healing of contaminated abdominal wounds in a dogmodel147. In contrast, de Holl et al. found an increased rate of in-fection after dead space closure in an animal model148. A meta-analysis of 875 patients was done to assess dead space woundclosure after cesarean delivery; it demonstrated 34% fewerwound complications with use of a layered closure, comparedwith the rate associated with closure of the skin only, when >2cm of subcutaneous adipose tissue was present149.

The proper management of dead space in orthopaedicpatients has not been clearly defined. Proper removal of in-

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fected or necrotic tissue, thorough irrigation, and appropriateantibiotic treatment improve wound-healing. There is evi-dence that subcuticular wound closure with monofilamentsutur minimizes tissue ischemia and is associated with de-creased bacterial contamination.

Surgical Dressing and Wound Careound dressings assist with healing by acting as a physicalbarrier to bacteria, immobilizing or splinting the wound

to protect it from subsequent injury, helping with hemostasis(i.e., pressure dressings), reducing dead space, and minimizingpain. Multiple studies have shown that, with the use of occlu-sive dressings, both re-epithelialization and subsequent col-lagen synthesis are two to six times faster than they are inwounds exposed to air150-154. On a cellular level, dressings assistwound-healing by creating a hypoxic wound environmentwherein fibroblasts proliferate and angiogenesis occurs morerapidly. The host’s defenses are thought to be improved underan occlusive dressing, and the creation of this hypoxic, acidicenvironment is thought to slow the growth of normal skinpathogens. Dressings act as a physical barrier to reduce the mi-gration of bacteria into the wound150. Hutchinson andMcGuckin, in a systematic review of 111 studies, found that therate of infection under occlusive dressings was lower than thatunder nonocclusive dressings (2.6% compared with 7.1%)155.Studies comparing nonbiologic occlusive dressings have sug-gested that, although their physical characteristics differ, theredoes not appear to be any clear benefit of one occlusive dress-ing over another. In a recent review of open and occlusivedressings, the authors recommended that surgical wounds becovered with a three-layer dressing156. The first layer, placed di-rectly on the wound, should be a non-adhering, hydrophilicdressing such as Adaptic (Johnson and Johnson, New Brun-swick, New Jersey) or Xeroform (Sherwood Medical Industries,Markham, Ontario, Canada). An absorptive layer (i.e., gauze)would be placed on the first layer. The third layer would be anocclusive material to adhere the dressing to the skin.

The proper timing of dressing removal is also controver-sial. Studies of clean and clean-contaminated wounds showedno difference in infection rates according to whether thedressing was removed on the first postoperative day or at thetime of suture removal157,158. After the dressing is removed, thewound may be cleaned with tap water or saline solution, butantiseptics such as hydrogen peroxide should be avoided.Showering may commence after wound epithelialization with-out an increased risk of infection150.

A variety of creams, ointments, and solutions have beenadvocated as means of propagating wound epithelialization.Cooper et al. evaluated the toxicity of several antimicrobialagents and found povidone-iodine to be significantly moretoxic to fibroblasts than other agents (p < 0.05)102. Kramershowed a detrimental effect of povidone-iodine on wound-healing103. Triple antibiotic ointment was shown to increasere-epithelialization by 25% in an animal model159. In a pro-spective, randomized, controlled trial evaluating 426 uncom-plicated wounds, the infection rates in the groups treated with

bacitracin ointment (six of 109, 5.5%) or triple antibioticointment (five of 110, 4.5%) were lower than those in thegroups treated with silver sulfadiazine (twelve of ninety-nine,12.1%) or petroleum (nineteen of 108, 17.6%) (p = 0.0034)160.Broad-spectrum ointments provide occlusion and increaseepithelialization while the wound heals.

The majority of evidence-based reports on wounddressings have been published in the plastic surgery and der-matology literature. Current recommendations for the man-agement of uninfected surgical wounds include the use of athree-layered surgical dressing. The use of a triple antibioticointment can be followed by application of a nonadherent,hydrophilic layer. The second layer should be absorptive, andthe final layer should be occlusive to contain the underlyingphysiologic milieu. The dressing may be removed as early asthe first postoperative day, and the wound may be gentlycleaned with water or saline solution (Table IV).

Operating Roomne area of infection prevention that is often overlookedis the operating room itself. Several studies have shown

that improvements in airflow and ultraviolet lighting reducenot only bacterial counts but also rates of surgical site infec-tion. A cohort study by Knobben et al.161 demonstrated that,compared with use of conventional airflow systems, use of alaminar-flow operating theater significantly decreased therates of bacterial wound contamination (p = 0.001), pro-longed wound discharge (p = 0.002), and superficial infec-tion of the surgical site (p = 0.004). A retrospective study byGruenberg et al. showed that conducting spinal fusions invertical laminar-flow operating rooms dramatically reducedthe rate of wound infections (zero of forty patients) com-pared with that following procedures conducted in conven-tionally ventilated operating rooms (eighteen [13%] of 139patients, p < 0.017)162. Hansen et al. sampled operative fieldsin laminar-flow rooms and found them to be, on the average,twenty times less contaminated than operative fields in com-parable rooms without laminar flow (Table III)163.

The use of ultraviolet light as a means of reducing theairborne bacterial burden and possibly the rate of wound in-fections has also been studied. Multiple basic-science studieshave shown that ultraviolet light decreases the numbers ofcolony-forming units164,165. Berg et al. found ultraviolet lightto be even more effective than a laminar-flow ventilationsystem in decreasing airborne bacterial load166,167. Modernhigh-volume exchange in operating rooms has resulted inequivalent levels of colony-forming units and decreased thebenefit of ultraviolet light.

We are not aware of any Level-I clinical data on operat-ing-room issues of clothing type, body exhaust, number ofpersonnel, and conversation in operating rooms. Severalwell-performed basic-science studies have demonstrated in-creases in colony-forming units in operating rooms, whichmight be extrapolated as increasing the risk of deep infection.Critical wound contamination most likely results from air-borne bacteria or residual bacteria on the skin after cleaning.

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The greatest source of airborne bacteria is the operating-room personnel, with ears and beards being the two areasmost likely to shed bacteria168. Bethune et al. found that menshed a greater number of bacteria per minute than post-menopausal women, and premenopausal women shed evenfewer bacteria169. The number of bacteria shed by operating-room personnel can be decreased by using air exhaust sys-tems or completely covering ears and beards168. If operating-room-personnel exhaust systems are not feasible, the dress ofthe personnel can influence the number of colony-formingunits grown on culture of specimens obtained in operatingrooms. The use of wraparound gowns and synthetic gownsdecreases the number of colony-forming units comparedwith that associated with the use of cotton gowns or operating-room clothing170. Blom et al. recommended the use of non-woven disposable drapes or woven drapes with an imperme-able layer below them for surgical draping171. Ritter indicatedthat the average number of colony-forming units in an oper-ating room was increased from 13.4 to 24.8 when the doorswere left open and that intermittent opening of doors did notsignificantly decrease the number of colony-forming unitscompared with that measured when the doors were left open172.Implants have also been shown to be associated with a higherrate of positive cultures if left outside their packaging in theoperating room for more than two hours173.

In addition to the above prophylactic measures, there isexcellent evidence that surgical site infection can be decreasedby close control of perioperative glucose levels, especially inpatients with diabetes174-179; by maximizing patient oxygenationin the first twenty-four hours perioperatively180-183; and bymaintaining patient normothermia in the perioperative pe-riod (Table III)184. Forty-four hospitals reported data on more

than 35,000 patients during a trial to maximize control of glu-cose, oxygenation, and normothermia in the postoperativesetting. Over the course of the study, the infection rate de-creased 27%, from 2.3% to 1.7%. Thus, a surgical infectionoccurred in 200 fewer patients in these hospitals.

Overviewhere are significant data that can help surgeons to de-crease the risk of perioperative surgical site infections. We

reviewed the best available literature and made recommenda-tions in an attempt to help orthopaedic surgeons to minimizesurgical site infections in their patients.

AppendixTables listing important evidence-based articles on pre-operative antibiotics, surgical scrubs, and use of surgical

drains; a table presenting the Gustilo and Anderson classifica-tion system for open fractures; and a table listing the activitiesof antiseptic agents are available with the electronic versionsof this article, on our web site at jbjs.org (go to the article cita-tion and click on “Supplementary Material”) and on ourquarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

Nicholas Fletcher, MDD’Mitri Sofianos, BSMarschall Brantling Berkes, BSWilliam T. Obremskey, MD, MPHVanderbilt Orthopedic Trauma, Medical Center East–South Tower, Suite 4200, Nashville, TN 37232-8774. E-mail address for W.T. Obremskey: [email protected]

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Prevention of Perioperative Infection · Prevention of Perioperative Infection By Nicholas Fletcher, MD, D’Mitri Sofianos, BS, Marschall Brantling Berkes, BS, and William T. Obremskey,